Laboratory of Molecular NeuroTherapeutics
PI: Tsuneya Ikezu, M.D., Ph.D.
The Laboratory of Molecular NeuroTherapeutics mainly focuses on neuroimmune cell-mediated regulations of neuronal function, neurogenesis, neuroinflammation, and neurodegeneration. In particular, we are interested in how the innate immune-related molecules in the central nervous system (CNS) influences the pathology and progression of select neurodegenerative disorders e.g. Alzheimer’s Disease, Frontotemporal Dementia, NeuroAIDS, and recently Chronic Traumatic Encephalopathy.
Current studies include pharmacological means to suppress the innate immune response in the CNS with the goal of enhancing neuronal protection, and minimizing collateral damage from an activated immune response in the CNS. Specifically, we are investigating the role of the signaling cytokine IL-4/10/CD200 and its potential anti-inflammatory and neuroprotective role between microglia and both neurons and astrocytes during active CNS inflammation. Further, we are exploring IL-4/10/CD200 as a potential therapeutic in chronic inflammatory states within the CNS, such as seen in Alzheimer’s disease, to minimize neuronal cell loss.
A second focus of our lab is the investigation of tau-tubulin kinases (TTBK1 and 2) and their role in protein phosporylation leading to the formation of tau and alpha-synuclein aggregates within neurons, a key pathology observed in AD, Amyotrophic Lateral Sclerosis, Spinocerebellar Ataxia, and Frontotemporal Dementia . We are currently performing a cutting-edge drug discovery program to identify potential inhibitors to TTBK1 with the goal of identifying potential new therapeutic(s) that could prevent tangle formation within neurons in these neurodegenerative states. We primarily use novel gene-targeted/transgenic mouse models to characterize our studies by employing a mix of assays including: standard biochemical assays, gene expression analyses, tissue cultures from both primary cells and cell lines, immunohistochemistry, gene-delivery vectors, and animal behavioral testing.